The formation of C—X bonds, where X is for example C, S, N, B, O, Sn and Si, is crucial in chemical synthesis and some of the most powerful methodologies to create these bonds are cross-coupling reactions. Over the last thirty years, the development of transition metal catalyzed cross-coupling reactions has transformed the way these bonds are created (Metal-Catalyzed Cross-Coupling Reactions, 2 ed. [Eds.: A. de Meijere, F. Diederich), Wiley-VCH, Weinheim, (2004); Handbook of Organopalladium Chemistry for Organic Synthesis, ed. (Ed.: E. Negishi), John Wiley & Sons, New York, (2002)].
Within the current arsenal of transition metal catalyzed cross-coupling protocols, palladium processes are amongst the most widely employed and include Hiyama [Y. Hatanaka, T. Hiyama, J. Org. Chem. (1988), 53, 918], Kumada [K. Tamao, K. Sumitani, M. Kumada, J. Am. Chem. Soc. (1972), 94, 4374], Negishi [E. Negishi, A. O. King, N. Okukado, J. Org. Chem. (1977), 42, 1821; A. O. King, N. Okukado, E. Negishi, Chem. Commun. (1977), 683], Suzuki [N. Miyaura, K. Yamada, A. Suzuki, Tetrahedron Lett. (1979), 20, 3437] and Stille [D. Milstein, J. K. Stille, J. Am. Chem. Soc. (1978), 100, 3636] reactions. In spite of tremendous progress in the developments of general methods to couple aryl and alkenyl halides, the use of alkyl halides remained a longstanding challenge, until the advent of bulky, electron rich phosphine ligands. In fact, central to the success of these transformations are palladium metal centers ligated most often with tertiary phosphines or, recently N-heterocyclic carbenes. Unfortunately, phosphines are air sensitive and some even pyrophoric. Furthermore, because active palladium (0) complexes are unstable and normally decompose with time, most protocols involve in situ formation of the catalyst.
Although yearly improvements to the supporting ligands have been made [A. Zapf, M. Beller, Chem. Commun. (2005), 431; T. E. Barder, S. D. Walker, J. R. Martinelli, S. L. Buchwald, J. Am. Chem. Soc. (2005), 127, 4685; C. J. O'Brien, E. A. B. Kantchev, G. A. Chass, N. Hadei, A. C. Hopkinson, M. G. Organ, D. H. Setiadi, T. H. Tang, D. C. Fang, Tetrahedron (2005), 61, 9723; J. E. Milne, S. L. Buchwald, J. Am. Chem. Soc. (2004), 126, 13028; T. Brenstrum, D. A. Gerristma, G. M. Adjabeng, C. S. Frampton, J. Britten, A. J. Robertson, J. McNulty, A. Capretta, J. Org. Chem. (2004), 69, 7635; T. Brenstrum, D. A. Gerristma, G. M. Adjabeng, C. S. Frampton, J. Britten, A. J. Robertson, J. McNulty, A. Capretta, J. Org. Chem. (2004), 69, 7635; J. H. Kirchhoff, C. Dai, G. C. Fu, Angew. Chem. (2002), 114, 2025; Angew. Chem. Int. Ed. (2002), 41, 1945; M. R. Netherton, G. C. Fu, Angew. Chem. (2002), 114, 4066; Angew. Chem. Int. Ed. (2002), 41, 3910; G. A. Grasa, M. S. Viciu, J. Huang, C. Zhang, M. L. Trudell, S. P. Nolan, Organometallics (2002), 21, 2866; M. R. Netherton, C. Dai, K. Neuschütz, G. C. Fu, J. Am. Chem. Soc. (2001), 123, 10099], advanced ligands [A. C. Frisch, M. Beller, Angew. Chem. (2005), 117, 680; Angew. Chem. Int. Ed. (2005), 44, 674] are still under-used mainly due to sensitivity, difficulty-of-use, limited availability and expense. Indeed, most synthetic chemists still rely on the reasonably versatile Pd(PPh3)4, first synthesized by Malatesta and Angoletta in 1957 [L. Malatesta, M. Angoletta, J. Chem. Soc. (1957), 1186].
As mentioned above, recently, an alternative to the “tried and tested” phosphine ligands has emerged. N-Heterocyclic carbenes (NHC) have attracted considerable interest as ligands for transition metal homogeneous catalysis. Due to their excellent α-donor properties and their variable steric bulk, NHC ligands impart excellent activity and thermal stability to the catalysts formed. The groups of Beller [R. Jackstell, M. G. Andreu, A. C. Frisch, K. Selvakumar, A. Zapf, H. Klein, A. Spannenberg, D. Röttger, O. Briel, R. Karch, M. Beller, Angew. Chem. (2002), 114, 1028; Angew. Chem. Int. Ed. (2002), 41, 986; A. C. Frisch, F. Rataboul, A. Zapf, M. Beller, J. Organomet. Chem. (2003), 687, 403], Herrmann [G. D. Frey, J. Schütz, E. Herdtweck, W. A. Herrmann, Organometallics (2005), 24, 4416; C. W. K. Gstöttmayr, V. P. W. Böhm, E. Herdtweck, M. Grosche, W. A. Herrmann, Angew. Chem. (2002), 114, 1421; Angew. Chem. Int. Ed. (2002), 41, 1363; W. A. Herrmann, C.-P. Reisinger, M. Spiegler, J. Organomet. Chem. (1998), 557, 93], Nolan [O. Navarro, N. Marion, N. M. Scott, J. Gonzalez, D. Amoroso, A. Bell, S. P. Nolan, Tetrahedron (2005), 61, 9716; R. Singh, M. S. Viciu, N. Kramareva, O. Navarro, S. P. Nolan, Org. Lett. (2005), 7, 1829; H. Lebel, M. K. Janes, A. B. Charette, S. P. Nolan, J. Am. Chem. Soc. (2004), 126, 5046; M. S. Viciu, E. D. Stevens, J. L. Petersen, S. P. Nolan, Organometallics (2004), 23, 3752; M. S. Viciu, O. Navarro, R. F. Germaneau, R. A. Kelly III, W. Sommer, N. Marion, E. D. Stevens, C. Luigi, S. P. Nolan, Organometallics (2004), 23, 1629; M. S. Viciu, R. A. Kelly, E. D. Stevens, F. Naud, M. Studer, S. P. Nolan, Org. Lett. (2003), 5, 1479] and Sigman [D. R. Jensen, M. J. Schultz, J. A. Mueller, M. S. Sigman, Angew. Chem. (2003), 115, 3940; Angew. Chem. Int. Ed. (2003), 42, 3810] have made significant progress towards the development of NHC-based palladium catalysts. However, when compared to processes utilizing phosphine ligands, the development of NHC-based protocols has been less successful. Indeed, palladium-NHC catalysts lack the substrate scope and ease-of-use of their phosphine cousins [Peris, E.; Crabtree, R. H. Coord. Chem. Rev. (2004), 248, 2239-2246; Crudden, C. M.; Allen, D. P. Coord. Chem. Rev. (2004), 248, 2247-2273; Herrmann, W. A.; Öfele, K.; v. Preysing, D.; Schneider, K. S. J. Organomet. Chem. (2003), 687, 229-248; Herrmann, W. A. Angew. Chem., Int. Ed. (2002), 41, 1290-1309]. The high sensitivity of isolated N-heterocyclic carbenes necessitates handling under rigorously anhydrous conditions, typically employing a glove-box. These factors make large scale production using these catalysts unattractive [Arentsen, K.; Caddick, S.; Cloke, F. G. N.; Herring, A. P.; Hitchcock, P. B. Tetrahedron Lett. (2004), 45, 3511-3515; Hadei, N.; Kantchev, E. A. B.; O'Brien, C. J.; Organ, M. G. Org. Lett. (2005), 7, 1991-1994; Arentsen, K.; Caddick, S.; Cloke, F. G. N. Tetrahedron (2005), 61, 9710-9715; Grasa, G. A.; Viciu, M. S.; Huang, J.; Zhang, C.; Trudell, M. L.; Nolan, S. P. Organometallics (2002), 21, 2866-2873]. In situ preparation of active Pd—NHC catalysts has been the dominant strategy to overcome these problems, however such strategies have been plagued with irreproducibility and wide yield variations [O'Brien, C. J.; Kantchev, E. A. B.; Chass, G. A.; Hadei, N.; Hopkinson, A. C.; Organ, M. G.; Setiadi, D. H.; Tang, T.-H.; Fang, D.-C. Tetrahedron (2005), 61, 9723-9735].
Palladium (II) complexes of N-ferrocenyl-substituted N-heterocyclic carbenes have been reported [Bertogg, A.; Camponovo. F.; Togni, A. Eur. J. Inorg. Chem. (2005), 347-356]. In this publication, an intermediate PdII species comprising a pyridine ligand was prepared, however due to its instability and the formation of dimeric species, this compound was converted to a complex containing a triphenylphosphine ligand and this complex was used in catalytic asymmetric amide cyclizations.
There is therefore a need for air-stable, easy-to-prepare-and-handle transition metal-heterocyclic carbene complexes that are readily activated under the reaction conditions for use in routine and industrial chemical synthesis.